Atopic allergic diseases range from the relatively minor, such as seasonal rhinitis and conjunctivitis, to the more serious, such as atopic dermatitis and atopic asthma, and life threatening, such as anaphylactic shock. Linking these conditions is the immune response of the body to allergens, which response involves the production of immunoglobulin E (IgE) antibodies in genetically predisposed individuals (atopy). Inhibition of IgE production has long been a goal in specific immunotherapy of allergic disease using desensitization vaccines. However, in recent years the safety and efficacy of vaccine therapy have been questioned, but the desire to reduce IgE levels has not waned.
Interleukin 4 (IL4) is a protein mediator in the lymphoid system. Studies of lymphocytes from atopic individuals have revealed the presence of higher than normal numbers of T lymphocytes with the ability to secrete IL4 in response to stimulation, and larger quantities of IL4 secreted following stimulation.
Anti-IL4 antibody has been found to inhibit IgE, but not IgG1 or IgG2, [Finkelman et al, Ann. Rev. Immunol., 8:303 (1990)], and the production of IL5 secreting T cells [Maggi et al, J. Immunol., 148:2142 (1992)]. Further, recent data suggests that IL4 may affect eosinophil accumulation in tissues. See, e.g. Tepper et al, Cell, 62:457 (1990); Tepper et al, Cell, 57:503 (1989).
There remains a need in the art for a high affinity IL4 antagonist, which would reduce eosinophil inflammation both by reducing the proliferation of IL5 secreting cells, and by inhibiting an adherence mechanism whereby eosinophils may be accumulating in tissues, and can be used to treat, prevent or diagnose allergic reactions.